Impact of pneumothorax on mortality, morbidity, and hospital resource utilization in COVID-19 patients: a propensity matched analysis of nationwide inpatient sample database

Background Spontaneous pneumothorax (PTX) is more prevalent among COVID-19 patients than other critically ill patients, but studies on this are limited. This study compared clinical characteristics and in-hospital outcomes among COVID-19 patients with concomitant PTX to provide insight into how PTX affects health care utilization and complications, which informs clinical decisions and healthcare resource allocation. Methods The 2020 Nationwide Inpatient Sample was used analyze patient demographics and outcomes, including age, race, sex, insurance status, median income, length of hospital stay, mortality rate, hospitalization costs, comorbidities, mechanical ventilation, and vasopressor support. Propensity score matching was employed for additional analysis. Results Among 1,572,815 COVID-19 patients, 1.41% had PTX. These patients incurred significantly higher hospitalization costs ($435,508 vs. $96,668, p < 0.001) and longer stays (23.6 days vs. 8.6 days, p < 0.001). In-hospital mortality was substantially elevated for PTX patients (65.8% vs. 14.4%, p < 0.001), with an adjusted odds ratio of 14.3 (95% CI 12.7–16.2). Additionally, these patients were more likely to require vasopressors (16.6% vs. 3.3%), mechanical circulatory support (3.5% vs. 0.3%), hemodialysis (16.6% vs. 5.6%), invasive mechanical ventilation (76.9% vs. 15.1%), non-invasive mechanical ventilation (19.1% vs. 5.8%), tracheostomy (13.3% vs. 1.1%), and chest tube placement (59.8% vs. 0.8%). Conclusions Our findings highlight the severe impact of PTX on COVID-19 patients, characterized by higher mortality, more complications, and increased resource utilization. Also, being Hispanic, male, or obese increased the risk of developing concomitant PTX with COVID-19. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-024-03161-z.


Background
Coronavirus disease is caused by a highly infectious pathogen infection and can present with minimal, non-specific symptoms [1,2].( Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory failure in the acute phase or as a post-Covid syndrome [3,4].
The Coronavirus Disease 2019 (COVID-19) has increased morbidity and mortality rates up to 40% in critically ill patients, and to combat this, we must understand the disease's complications, especially those that are potentially life-threatening [5,6].One such complication is pneumothorax (PTX), a condition observed in both spontaneously breathing patients and those on mechanical ventilation [7].PTX is a potentially crippling complication of COVID-19, with an average reported incidence ranging from 1 to 10%, depending on clinical severity [8,9].There are few studies that address the impact of PTX on morbidity, mortality, and resource utilization among COVID-19 patients, highlighting a significant gap in our understanding [10,11].
Before the COVID-19 pandemic, PTX was a common and potentially fatal complication in mechanically ventilated patients (MVPs) with acute respiratory distress syndrome (ARDS), with an overall 30-day mortality rate of 40% [12].Mortality was largely attributed to air leaks and acute lung injury.The traditionally high ventilatory volumes and high airway pressure in the diseased lungs caused volutrauma and barotrauma, respectively [13].The overall incidence of PTX decreased from 55 to 17% after the implementation of protective lung strategies [14].Other factors related to the occurrence of PTX include history of chronic pulmonary disease, smoking, and ARDS [15].
Research indicates a higher occurrence of PTX in COVID-19 patients independent of their mechanical ventilation status.COVID-19 patients on mechanical ventilation have higher rates of barotrauma and volutrauma progressing to PTX than patients with conventional ARDS or other viral pneumonias [16][17][18].Spontaneous PTX is more prevalent among COVID-19 patients than other critically ill individuals, with incidence rates ranging from 0.3 to 23.8% in the COVID-19 positive population [8,9,19,20].There are also reports of patients with non-severe COVID-19 developing spontaneous PTX [21][22][23].
We assessed the influence of PTX on COVID-19 patient mortality rates, morbidity, and healthcare resource utilization.A better understanding of the effect of PTX on COVID-19 patient prognosis will guide treatment of this high-risk cohort.The strategic implementation of preventative strategies may ultimately reduce hospital expenditures and improve outcomes in the COVID-19 positive population.

Methods
This was a retrospective study conducted using Nationwide Inpatient Sample (NIS) data from 2020.International classification of diseases 10th-clinical modification (ICD-10-CM) codes were used to retrieve patient samples with comorbid conditions, and ICD-10 procedure codes were used to identify inpatient procedures (Supplemental Table 1).All COVID-19 positive patients ≥ 18 years of age admitted to the hospital were included in this study.Variables were divided into patient-related, hospital-related, and indicators of illness severity.We collected patient age, race, sex, insurance status (Medicare, Medicaid, private insurance, self-payment, no charge), median income based on patient's zip code, and disposition.We also collected hospital location, teaching status, bed size, and region.Lastly, we collected data indicating illness severity, including length of stay (LOS), mortality, hospitalization cost, comorbidities, and treatment interventions.The primary outcome of our study was in-hospital mortality, and the secondary outcomes included intubation and mechanical ventilation, hemodialysis use, mechanical circulatory support use, vasopressor use, non-invasive ventilation, chest tube placement, tracheostomy, cardiovascular accident, cardiogenic shock, venous thromboembolism, acute liver failure, sudden cardiac arrest, LOS, the financial burden on healthcare, and resource utilization.

Statistical analysis
For descriptive statistics in Table 1, continuous variables are summarized as mean ± standard deviation (SD), and categorical data are expressed as numbers and percentages.We used the Rao-Scott Chi-square test for categorical variables (e.g., sex and risk factors) to assess the independence in Table 1, and a multivariate linear regression model for continuous variables (LOS and total hospitalization cost).Moreover, we developed a multivariable logistic regression model for each categorical variable in Table 2 to report adjusted odds ratios for the two cohorts.We used a threshold of p ≤ 0.20 to retain predictor variables in the multivariable logistic regression models and p ≤ 0.05 in the multivariate linear regression model.The multivariable logistic regression models and the multivariate linear regression model used hospital-related, Elixhauser comorbidities, and patient-related variables as predictors.Since, the control group (COVID-19 positive but PTX-negative) had a significantly higher sample than the test group (COVID-19 positive and PTX-positive), we conducted a secondary, propensity score matched analysis (PSM) to confirm results obtained on the raw samples.Baseline demographics (age, race, sex, income status, insurance status) were matched using a 1:1 nearest neighbor propensity score with 0.05 caliper width.On matched cohorts, the same analysis was repeated with the same regression models.The results from the PSM samples are reported in Tables 3 and 4. All analyses were performed using R, SAS, and Python programming language.

Demographics and patient characteristics
Our study included 1,572,815 individuals, with 22,230 (1.4%) in the PTX group and 1,550,585 (98.6%) in the non-PTX group (Table 1).The PTX group consisted of more Hispanic patients (31.8% vs. 21.3%) and fewer White patients (44.2% vs. 51.1%)than the non-PTX group (p < 0.001).The PTX group also had a higher proportion of males (65.8% vs. 51.6%,p < 0.001).Patient ages differed between both groups and sexes.There were more patients 50-69 years old in the PTX group (46.7% vs. 37.0%, p < 0.001).Additionally, the average age for females was slightly higher in the PTX group (65.9 years vs. 63.1 years), while it was almost identical for males across both groups.
There was a small difference in patient income between the two groups and no difference in insurance.There were more individuals earning less than $49,999 a year in the PTX group than in the non-PTX group (36.4% vs. 34.1%,p = 0.004).However, there were no substantial differences in insurance status between the two groups (p = 0.113).There were differences in hospital division distribution, bed size, and teaching status between the two groups.The West South-Central hospital division saw a significantly higher percentage of PTX cases (18.1% vs. 14.2%, p < 0.001).There was also a higher proportion of PTX patients at large hospitals (50.4% vs. 46.6%,p < 0.001) and urban, teaching hospitals (76.3% vs. 71.5%,p < 0.001).

In-hospital morbidity and mortality
In-hospital mortality between PTX and non-PTX COVID-19 patients differed significantly.Of the 1,550,585 non-PTX patients, 12.6% died in the hospital.This was markedly lower than the 65.8% mortality rate among the 22,230 PTX patients.The adjusted odds ratio (AOR) for in-hospital mortality was significantly high at 15.9 (95% CI 14.9-17.0),indicating a substantially higher risk of in-hospital death for PTX patients (Table 2).PSM of 44,460 COVID-19 patients (half with PTX, half without) revealed the in-hospital mortality rate was 14.4% for non-PTX patients but 65.8% for PTX patients.
Of note, the need for chest tube placement was remarkably higher among PTX patients at 59.8% compared to 0.6% in non-PTX patients, with an AOR of 244.9 (95% CI 226.3-265.1)(Table 2).Results from PSM showed increased rates of both tracheostomy placement (AOR 14.2, 95% CI 10.5-19.0)and chest tube placement (AOR 231.3, 95% CI 163.1-328.0)(Table 4).PSM showed similar trends for mechanical ventilation, with PTX patients having much higher rates of mechanical ventilation, even when separated into invasive (AOR of 23

In-hospital quality measures
The in-hospital quality measures of total charges for each patient and LOS were compared between the PTX and non-PTX cohorts.PTX patients required considerably more resources as reflected in total charges.The mean total hospitalization charge for PTX patients was notably higher than for non-PTX patients ($435,508 vs. $86,822), with a difference in adjusted total charge for PTX patients being $336,782 greater.The mean LOS was also extended for PTX patients at 23.6 days, compared to 7.8 days for non-PTX patients; the adjusted LOS was 15.3 days longer for PTX patients (Table 2).Data from PSM corroborated this trend: PTX patients had a significantly higher mean total hospitalization charge at $435,508 compared to $96,668 for non-PTX patients, which is an adjusted total charge of $320,978 more.Similarly, the mean LOS for PTX patients was 23.6 days, compared to 8.6 days for non-PTX patients, marking an adjusted LOS 14.9 days longer (Table 4).

Disposition
Hospital dispositions between the two groups differed significantly.More non-PTX patients left against medical advice (1.1% vs. 0.3%), were discharged to home health care (13.1% vs. 5.4%), were discharged routinely (51.5% vs. 7.6%), or were transferred to another care facility (18.6% vs. 16.4%).In contrast, more PTX patients were transferred to a short-term hospital (3.0% vs. 4.5%).PSM produced similar results in outcomes.For example, 0.9% of non-PTX patients left against medical advice compared to 0.3% of PTX patients.These differences, reflected in both AOR and PSM data, highlight the impact of PTX on the course of recovery in COVID-19 patients (Tables 2 and 4).

Discussion
We found that the average incidence of PTX in COVID-19 patients was 1.41% out of 1.5 million people affected in 2020, and patients who developed PTX had a significantly higher mortality rate, greater resource utilization, longer LOS, and higher costs of care.This cohort was more likely to be male, obese, and Hispanic, illuminating socioeconomic, racial, and gender disparities.Patients with PTX required more aggressive treatment interventions and had longer hospital stays, highlighting a need for COVID-19 prevention and treatment optimization to minimize the risks of developing PTX.COVID-19 positive individuals with PTX require more support, have longer hospital stays, have higher costs of care, and use more hospital resources.We found that this cohort was more likely to need mechanical circulatory support and interventions like chest tube placement, and were more likely to experience a long, complicated hospital stay that resulted in tracheostomies.Their mean LOS was nearly 15 days longer than the LOS of non-PTX patients.Previous studies have shown that critically ill patients with COVID-19 often require invasive procedures, including central venous access, that possess an additional risk of iatrogenic PTX [24].Wang et al. found that PTX was associated with high mortality, poor prognosis, and prolonged LOS [9].Costs of care are related to both the LOS and amount of support a patient requires; the PTX patients in our study had significantly higher costs of care than non-PTX patients, with an adjusted mean total hospitalization charge $320,977.60higher.
We also compared mortality between the two cohorts.We found that hospital mortality in COVID-19 patients with PTX admitted in US hospitals between January-December 2020 was nearly 14 times higher than in patients without this complication.Geraci and colleagues reported similar outcomes of a 58% mortality rate in PTX patients and 63% in MVPs [17].Similarly, in another multicenter study, the odds of mortality in patients with COVID-19 related PTX was 7.15 compared to those who did not have PTX [25].
PTX is closely correlated with a patient needing mechanical ventilation, and both are correlated with high mortality rates.The higher mortality rate in our study is associated with high rates of invasive mechanical ventilation (77% vs. 15%).These results are validated by a large multicenter study of 842 critically ill patients (71% MVPs) that showed that PTX patients had a higher mortality rate (63% vs. 49%, p = 0.04), with the odds of in-hospital death increased nearly two-fold [21].PTX patients often have more severe illness and spend more days on mechanical ventilation, placing them at higher risk of needing additional interventions, like tracheostomy and mechanical circulatory support [17,26].Invasive interventions increase the risk of multi-organ failure or organ damage, resulting in longer hospital stays and greater mortality [17].The extensive support needed by these patients highlights the value of understanding the causes of PTX so it can be prevented.
Understanding the pathophysiology of COVID-19-associated PTX may help us understand why this progression is associated with such high mortality rates.Developing COVID-19-associated PTX can be attributed to pathophysiological changes associated with COVID-19 and disease progression.One of the proposed pathological mechanisms, along with a COVID-19 hyperinflammatory state, include viral tropism to peripheral lung pneumocytes with a predisposition to peripheral bronchoalveolar communication, consequently leading to PTX and pneumomediastinum, along with barotrauma associated with positive-pressure ventilation [27].Contrary to this, studies have shown that PTX tends to occur later in the disease course when the hyperinflammatory state has decreased, likely from the dysregulation of lung repair [28].COVID-19 specific therapies potentially reduce viral clearance and interrupt the innate remodeling and repair process that may help prevent PTX [18].
Multiple factors are associated with developing PTX, including chronic pulmonary disease, smoking, previous history of lung disease, and prolonged intubation [20,28].Notably, both cohorts in our study had nearly identical rates of pre-existing comorbidities.However, contrary to most studies, there was a higher proportion of obese patients with COVID-19 and PTX.Obese patients are particularly at risk for developing COVID-ARDS and having poor outcomes [29].Although the association between body mass index (BMI) and PTX has not been established in patients with COVID-19, patients who develop spontaneous PTX tend to have a lower BMI [30].Similarly, a matched case-control study of 427 patients showed that PTX patients had a lower average BMI (22.4) than non-PTX patients (24.5), which falls under the lower range compared to our population [31].In contrast, a large study composed of 9800 COVID-19 patients, of which 67 developed PTX, two thirds of the affected patients had a BMI over 25 [10].Due to the conflicting evidence, additional research is needed to thoroughly assess the association between COVID-19, PTX, and other comorbidities.However, it can be hypothesized that obesity, being a well-established risk factor for severe C-ARDS, may increase the risk of complications, including PTX.
Determining a gender difference in the incidence of PTX associated with COVID-19 is complicated.The risk of primary spontaneous PTX is higher among males between the ages of 25-34 years, with risk increasing with patient height [32].In our study, males were nearly two times more likely to develop PTX than females.One reason for such differences could be the overall incidence and severity of COVID-19 being higher in the male population than the female population [33].The Centers for Disease Control and Prevention suggests the psychological, social, and behavioral differences in males may play an important role in overall exposure of SARS-COV-2, comorbidities (e.g., smoking), treatment initiation, compliance, and overall mortality [34].Smaller retrospective  and risk stratify the gender difference in incidence and outcomes associated with PTX.
The COVID-19 pandemic has highlighted long-standing, broad, and pervasive inequities between racial and ethnic minorities.Although the White population overall was most affected, Hispanic patients who were affected by COVID-19 had higher rates of PTX compared to other ethnicities (32% vs. 21%, p < 0.001).Racial and ethnic minorities often face barriers to healthcare, including socioeconomic factors, overcrowded living situations, high pre-existing comorbidities, systemic implicit bias, and vaccine disparities.These barriers can lead to high COVID-19 rates and thus, high ICU admission ratesshedding light on the rates of complicated COVID-19-ARDS in the Hispanic population [39,40].Further research is imperative to gain a more comprehensive understanding of the racial distribution of COVID-19.While existing studies have highlighted disparities in infection rates, severity of illness, and mortality among different racial and ethnic groups, there are still many unanswered questions and evolving dynamics, including vaccine equity and intersectionality.

Limitations
There are several limitations of our study to consider, including inherent limitations due to the retrospective nature of the study.One significant limitation is the inability to determine the exact timing of PTX in relation to the initiation of mechanical ventilation, owing to the constraints of the database used.Furthermore, the NIS database employed for this research is administrative in nature, which may not fully encapsulate the intricate details of a patient's hospitalization, such as history, physical examination findings, laboratory values, and imaging/pathological investigation reports.Additionally, these inpatient outcomes may not accurately reflect outpatient trends.It is also crucial to emphasize that these results were compiled prior to the development and widespread administration of effective COVID-19 vaccines.As such, they may not accurately depict current hospitalization patterns in the era of COVID-19 vaccination.

Conclusions
In our comprehensive analysis of 1.5 million COVID-19 patients during the year 2020, a significant association was established between the presence of PTX and a multitude of adverse outcomes.Specifically, COVID-19 patients who developed PTX exhibited elevated rates of in-hospital mortality, increased reliance on mechanical ventilation, greater vasopressor use, heightened occurrence of AKI, venous thromboembolism, and cerebrovascular accidents, as well as elevated procedural intervention rates, causing increased resource utilization.Risk factors for COVID-19 patients developing PTX were being Hispanic, male, or obese.These findings collectively underscore the profound impact of PTX in the context of COVID-19, emphasizing the critical need for early recognition, preventative measures, and optimized management to mitigate the associated risks, reduce treatment costs, and improve patient outcomes.

Table 2
In-hospital outcomes for patients with COVID-19 without pneumothorax and COVID-19 with pneumothorax